| Function/process | Mechanism/complexes and key partners | Key experimental evidence (assay/model) | Notes on selectivity vs BECN1 | Primary citation with year, DOI, URL |
|---|---|---|---|---|
| Identity / core annotation | Human **BECN2 / Beclin-2** is a mammal-specific Beclin-family paralog of BECN1; reported as ~431 aa in structural work and ~447 aa/predicted ~49 kDa in the discovery paper; contains Beclin-family **BH3-like region, coiled-coil domain (CCD), and C-terminal evolutionarily conserved/BARA-like domain**; acts as a scaffold in membrane-trafficking/autophagy pathways (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000005) | Sequence/domain comparison, immunoblot detection, phylogenetic/genomic analysis in human and mouse; co-IP with Beclin-network factors (pqac-00000001, pqac-00000004) | Distinct from BECN1 by mammal-specific origin, divergent N-terminus, stronger AMBRA1 binding, lack of Rubicon binding, and constitutive BCL2 association under starvation conditions (pqac-00000000, pqac-00000004, pqac-00000005) | **He et al., 2013**. DOI: 10.1016/j.cell.2013.07.035. URL: https://doi.org/10.1016/j.cell.2013.07.035 (pqac-00000001, pqac-00000002) |
| Canonical/autophagy-supporting scaffold role | BECN2 associates with **class III PI3K/PtdIns3K complex** components including **PIK3C3/VPS34, PIK3R4/VPS15 (p150), ATG14, UVRAG, AMBRA1**, supporting autophagosome biogenesis and autophagic flux (pqac-00000010, pqac-00000014) | Co-immunoprecipitation, structural CCD studies, Becn2 knockdown/knockout cells and mice showing reduced autophagy markers, reduced long-lived protein degradation, fewer autophagic structures, altered LC3/p62 readouts (pqac-00000009, pqac-00000014) | BECN2 overlaps with BECN1 in autophagy initiation but is biochemically distinct: stronger AMBRA1 interaction, no Rubicon co-IP, and starvation does not disrupt BECN2-BCL2 interaction as reported for BECN1-regulated complexes (pqac-00000012, pqac-00000014) | **Su et al., 2017**. DOI: 10.1002/pro.3140. URL: https://doi.org/10.1002/pro.3140 (pqac-00000014) |
| Ligand-induced lysosomal degradation of select GPCRs | BECN2 binds **GPRASP1/GASP1** via an N-terminal region including aa 69-88 and promotes post-endosomal sorting of GASP1-associated GPCRs to **LAMP1+ lysosomes**; cargos include **OPRD1/DOR, CNR1/CB1R, DRD2/D2R** and other GASP1-regulated receptors (pqac-00000009, pqac-00000010, pqac-00000027) | Yeast two-hybrid and co-IP for BECN2-GASP1 binding; receptor internalization/degradation assays; microscopy showing receptor retention in **EEA1+ early endosomes** and failure to reach lysosomes after BECN2 loss; rescue by WT but not GASP1-binding-defective BECN2 mutants (pqac-00000009, pqac-00000027) | This GPCR-trafficking role is a major BECN2-specific distinction: **BECN1, VPS34, and ATG14 knockdown did not phenocopy BECN2 loss** in the original GPCR degradation assays, supporting a separable trafficking function beyond shared autophagy roles (pqac-00000009, pqac-00000005) | **He et al., 2013**. DOI: 10.1016/j.cell.2013.07.035. URL: https://doi.org/10.1016/j.cell.2013.07.035 (pqac-00000009, pqac-00000027) |
| Structural basis of autophagy/trafficking selectivity | BECN2 CCD forms a **metastable antiparallel homodimer** with imperfect interface residues and also a **BECN2-ATG14 heterodimer**; this structural plasticity supports selective assembly of BECN2-containing complexes for autophagy and endolysosomal trafficking (pqac-00000003, pqac-00000023) | Crystal structures of BECN2 CCD and BECN2-ATG14 CCD complex; mutational/biophysical analyses showing weaker homodimer but tighter ATG14 binding; function tested in receptor degradation assays (pqac-00000003, pqac-00000014, pqac-00000023) | 2023 work argues **BECN2-ATG14** is especially important for BECN2-specific cargo handling, whereas **BECN1-UVRAG** is more important for EGFR trafficking; thus similar Beclin architectures support non-identical cargo selectivity (pqac-00000023) | **Qiu et al., 2023**. DOI: 10.1080/15548627.2023.2233872. URL: https://doi.org/10.1080/15548627.2023.2233872 (pqac-00000023) |
| Selective endolysosomal degradation of DRD2 and other GPRASP1-associated GPCRs | Potent **BECN2-ATG14** interaction is selectively required for degradation of **GPRASP1-associated GPCRs**, especially **DRD2/D2R**; BECN2 N-terminus binds GPRASP1 while the CCD engages ATG14 to support trafficking/degradation (pqac-00000010, pqac-00000023) | Functional mutagenesis plus receptor degradation assays in cells; comparison with EGFR cargo; stapled peptide enhancers of BECN2-ATG14 interaction tested for effects on autophagy and DRD2 turnover (pqac-00000010, pqac-00000023) | Clear cargo selectivity versus BECN1: **EGFR** depends more on **BECN1-UVRAG**, whereas **DRD2** depends more on **BECN2-ATG14** (pqac-00000023) | **Qiu et al., 2023**. DOI: 10.1080/15548627.2023.2233872. URL: https://doi.org/10.1080/15548627.2023.2233872 (pqac-00000023) |
| Chemical/biophysical modulation of BECN2 function | 2023 study designed **stapled peptides** that selectively bind the BECN2 CCD and enhance **BECN2-ATG14** interaction, increasing **BECN2-dependent autophagy** and **DRD2 degradation** without altering BECN1-dependent EGFR turnover (pqac-00000010, pqac-00000023) | Structural design, peptide binding, cellular autophagy assays, and cargo degradation assays for DRD2 versus EGFR (pqac-00000023) | Provides one of the first selective BECN2-directed modulatory strategies rather than pan-autophagy manipulation; experimental support is preclinical/cell-based (pqac-00000023) | **Qiu et al., 2023**. DOI: 10.1080/15548627.2023.2233872. URL: https://doi.org/10.1080/15548627.2023.2233872 (pqac-00000023) |
| Mitophagy and autophagosome formation: divergence from BECN1 | BECN2 contributes to basal/stress autophagosome formation in some settings, but **selective mitophagy** is chiefly a **BECN1** function linked to **ULK1-phosphorylated Ser15** and localization to **mitochondria-associated membranes (MAMs)**; BECN2 does not substitute for this mitophagy-specific role (pqac-00000026) | BECN1/BECN2 knockout HeLa cells and MEFs; mitophagy assays after mitochondrial damage; localization analyses at MAMs; rescue experiments with BECN1 variants (pqac-00000026) | Major 2023 clarification: BECN2 is not simply redundant with BECN1; **BECN1 loss impairs mitophagy**, whereas **BECN2 loss does not** in the same assays (pqac-00000026) | **Quiles et al., 2023**. DOI: 10.1126/scisignal.abo4457. URL: https://doi.org/10.1126/scisignal.abo4457 (pqac-00000026) |
| Noncanonical degradation of inflammasome sensors | BECN2 negatively regulates **NLRP3, AIM2, NLRP1, NLRC4** by promoting their lysosomal degradation through a **ULK1- and ATG9A-dependent, but BECN1/ATG16L1/LC3-independent** pathway; BECN2 recruits sensors to **ATG9A+ vesicles** and cooperates with **SEC22A, STX5, STX6** (pqac-00000015, pqac-00000017, pqac-00000019, pqac-00000021) | CRISPR/KO macrophages and THP-1 cells; co-IP and colocalization; half-life and inhibitor studies showing lysosome dependence; inflammasome activation readouts (IL1B, CASP1 cleavage); alum-induced peritonitis in mice (pqac-00000015, pqac-00000017, pqac-00000021) | This pathway is explicitly **noncanonical** and largely independent of canonical BECN1-LC3 autophagy machinery, underscoring a unique BECN2 degradative route in innate immunity (pqac-00000017, pqac-00000018, pqac-00000021) | **Deng et al., 2022**. DOI: 10.1080/15548627.2021.1934270. URL: https://doi.org/10.1080/15548627.2021.1934270 (pqac-00000015, pqac-00000017) |
| Negative regulation of MAPK/NF-kB inflammatory signaling | BECN2 targets **MEKK3/MAP3K3** and **TAK1/MAP3K7** for degradation via **ULK1-ATG9A**-dependent noncanonical autophagy; this suppresses **ERK1/2, NF-kB, and STAT3-linked inflammatory outputs** (pqac-00000016, pqac-00000020, pqac-00000022) | Endogenous interaction assays; gain/loss of BECN2 in innate immune cells; protein-versus-mRNA comparisons showing post-translational control; lysosome/autophagy inhibitor studies; genetic rescue by myeloid **Map3k3** ablation (pqac-00000016, pqac-00000020, pqac-00000022) | Again distinct from canonical BECN1 autophagy: degradation reported as **ATG9A-dependent but BECN1-, ATG16L-, and LC3-independent** (pqac-00000016, pqac-00000020) | **Zhu et al., 2020**. DOI: 10.1172/JCI133283. URL: https://doi.org/10.1172/jci133283 (pqac-00000016, pqac-00000020) |
| In vivo immune/tumor phenotypes | Loss of Becn2 in mice causes **splenomegaly, lymphadenopathy, increased inflammatory cytokines, persistent STAT3 activation, and higher lymphoma incidence**; BECN2 thus behaves as a suppressor of inflammation-driven tumorigenesis in these models (pqac-00000016, pqac-00000020) | Whole-animal knockout phenotyping, cytokine measurements, histology, and genetic rescue through **Map3k3** deletion in myeloid cells (pqac-00000016) | These phenotypes have not been attributed equivalently to BECN1 in the cited work and are mechanistically tied to the BECN2-specific ATG9A route (pqac-00000016) | **Zhu et al., 2020**. DOI: 10.1172/JCI133283. URL: https://doi.org/10.1172/jci133283 (pqac-00000016) |
| Metabolic physiology / receptor homeostasis | Becn2 insufficiency impairs autophagy in vivo and increases brain **CB1R/CNR1** abundance with **hyperphagia, obesity, and insulin resistance**; metabolic effects are thought to relate in part to receptor turnover and autophagic regulation (pqac-00000004, pqac-00000023) | Heterozygous and knockout mouse phenotyping; receptor abundance measurements and metabolic characterization (pqac-00000004, pqac-00000023) | Phenotype highlights that BECN2 has physiologic roles not fully captured by BECN1-centric autophagy models, especially via selective GPCR regulation (pqac-00000005, pqac-00000023) | **He et al., 2013**. DOI: 10.1016/j.cell.2013.07.035. URL: https://doi.org/10.1016/j.cell.2013.07.035 (pqac-00000009) |
| 2024 disease-model application: cartilage endplate degeneration | In LPS-treated chondrocyte/ATDC5 and lumbar disc degeneration models, **sesamin** upregulated **BECN2**, improving viability and reducing apoptosis; reported downstream effects included lower **ATG14, VPS34, GASP1**, reduced autophagy markers, and lower inflammasome proteins (**NLRP3, NLRC4, NLRP1, AIM2**) (pqac-00000024) | Transcriptomics, adenoviral BECN2 overexpression/knockdown, viability/apoptosis assays, autophagy readouts, and in vivo LDD model (pqac-00000024) | Useful as a recent disease-model application, but interpretation should be cautious because some reported directionality (higher BECN2 with lower autophagy) differs from foundational BECN2 autophagy literature (pqac-00000024, pqac-00000009) | **Zhang et al., 2024**. DOI: 10.18632/aging.205386. URL: https://doi.org/10.18632/aging.205386 (pqac-00000024) |
| 2024 expert synthesis on nonautophagic ATG functions | Review literature positions BECN2 as an example of an autophagy-related protein with important **noncanonical/nonautophagic trafficking and immune functions**, especially GPCR sorting through GPRASP1 and inflammatory control beyond canonical LC3 pathways (pqac-00000025) | Narrative expert review integrating primary studies on GPCR trafficking, immune regulation, and signaling functions of ATG proteins (pqac-00000025) | Reinforces that BECN2 should not be annotated only as a generic autophagy factor; it has distinct cargo-sorting and signaling roles relative to BECN1 (pqac-00000025) | **Shang et al., 2024**. DOI: 10.1080/15548627.2023.2254664. URL: https://doi.org/10.1080/15548627.2023.2254664 (pqac-00000025) |


*Table: This table summarizes experimentally supported functions, mechanisms, selectivity, and recent updates for human BECN2/Beclin-2. It is useful as a compact evidence map linking core biology to specific assays, pathways, and citations.*